Background & Aims: Ectopic pregnancy currently is the leading cause of pregnancy-related death during the first trimester. The methotrexate (MTX) was accepted as medical treatment and reduced surgery in unruptured ectopic pregnancy. Despite numerous studies, the best protocol for MTX treatment remains controversial. The present study compares single and two dose MTX administrations protocol in treatment of ectopic pregnancy.

Materials & Methods: In this prospective randomized clinical trial 100 eligible women that clinical examination and vaginal sonography confirmed the diagnosis of unruptured ectopic pregnancy, were collected in two groups (Singleand double dose). All patients received a dose (50mg/m2) in day 0 and only case group received same dose in day4. All women were given additional doses of MTX on day 7 and/or 11 and/or 14 if βhCG levels did not decrease by 15% during follow –up period. Results of two groups were compared for fall of serum βhCG , treatment response and adverse events.

Results: In the single dose group, treatment was considered successful in 44 women (88%), whereas in the two dose group, 46 women (92%) responded to treatment. In the two dose group fewer or 1 women (2%) experienced tubal rupture compared to 6 (12%) of those who had single doses. Other laboratory and clinical complications were not significant in two groups.

Conclusion: A first week two dose methotrexate regimen for the treatment of unruptured tubal ectopic pregnancy is more effective than a single dose. In addition, single dose have more treatment failure and cause more tubal rupture.